Imide and lactam derivatives of N-benzylpyroglutamyl-L-phenylalanine as VCAM/VLA-4 antagonists

Bioorg Med Chem Lett. 2001 Jan 8;11(1):1-4. doi: 10.1016/s0960-894x(00)00582-5.

Abstract

A series of imides and lactams derived from 4-amino-N-benzylpyroglutamyl-L-phenylalanine was prepared and evaluated for activity as VCAM/VLA-4 antagonists. Imides were more potent than the corresponding lactams; several had subnanomolar IC50s in an ELISA based assay and were also highly effective at blocking VLA-4 expressing Ramos cell binding to VCAM coated plates.

MeSH terms

  • Cell Adhesion / drug effects
  • Dipeptides / chemistry*
  • Dipeptides / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Imides / chemistry
  • Imides / pharmacology*
  • Inhibitory Concentration 50
  • Integrin alpha4beta1
  • Integrins / antagonists & inhibitors*
  • Lactams / chemistry
  • Lactams / pharmacology*
  • Molecular Structure
  • Phenylalanine / analogs & derivatives*
  • Pyrrolidonecarboxylic Acid / analogs & derivatives*
  • Receptors, Lymphocyte Homing / antagonists & inhibitors*
  • Tumor Cells, Cultured

Substances

  • Dipeptides
  • Imides
  • Integrin alpha4beta1
  • Integrins
  • Lactams
  • Receptors, Lymphocyte Homing
  • Phenylalanine
  • Pyrrolidonecarboxylic Acid